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首页> 外文期刊>Journal of cellular biochemistry. >CCAAT/Enhancer binding protein delta (c/EBPdelta) regulation and expression in human mammary epithelial cells: I. 'Loss of function' alterations in the c/EBPdelta growth inhibitory pathway in breast cancer cell lines.
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CCAAT/Enhancer binding protein delta (c/EBPdelta) regulation and expression in human mammary epithelial cells: I. 'Loss of function' alterations in the c/EBPdelta growth inhibitory pathway in breast cancer cell lines.

机译：CCAAT /增强子结合蛋白δ（c / EBPdelta）在人乳腺上皮细胞中的调节和表达：I.乳腺癌细胞系中c / EBPdelta生长抑制途径的“功能丧失”改变。

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"Loss of function" alterations in growth inhibitory signal transduction pathways are common in cancer cells. In this study, we show that growth arrest (GA) treatments--serum and growth factor withdrawal and growth inhibitory IL-6 family cytokines (Interleukin-6 and Oncostatin M (OSM))--increase STAT3 phosphorylation (pSTAT3), increase CCAAT enhancer binding protein delta (C/EBPdelta) gene expression and induce GA of primary, finite-lifespan human mammary epithelial cells (HMECs), and immortalized breast cell lines (MCF-10A and MCF-12A). In contrast, serum and growth factor withdrawal from human breast cancer cell lines (MCF-7, SK-BR-3, T-47D, and MDA-MB-231) for up to 48 h induced a relatively modest increase in pSTAT3 levels and C/EBPdelta gene expression and resulted in varying levels of GA. In most breast cancer cell lines, IL-6 family cytokine treatment increased pSTAT3 levels and C/EBPdelta gene expression, however, growth inhibition was cell line dependent. In addition to "loss of function" alterations in growth inhibitory pathways, breast cancer cell lines also exhibit "gain of function" alterations in growth signaling pathways. The Akt growth/ survival pathway is constitutively activated in T-47D and MCF-7 breast cancer cells. The Akt inhibitor LY 294,002 significantly enhanced T-47D growth inhibition by serum and growth factor withdrawal or IL-6 family cytokine treatment. Finally, we show that activation of the pSTAT3/C/EBPdelta growth control pathway is independent of estrogen receptor status. These results demonstrate that "loss of function" alterations in the pSTAT3/C/EBPdelta growth inhibitory signal transduction pathway are relatively common in human breast cancer cell lines. Defective activation of the pSTAT3/ C/EBPdelta growth inhibitory signal transduction pathway, in conjunction with constitutive activation of the Akt growth stimulatory pathway, may play a synergistic role in the etiology or progression of breast cancer.
机译：生长抑制信号转导途径中的“功能丧失”改变在癌细胞中很常见。在这项研究中，我们显示了生长停滞（GA）治疗-血清和生长因子停药以及生长抑制性IL-6家族细胞因子（白介素6和肿瘤抑制素M（OSM））-增加STAT3磷酸化（pSTAT3），增加CCAAT增强子结合蛋白δ（C / EBPdelta）基因表达并诱导原代，有限寿命的人乳腺上皮细胞（HMEC）和永生化的乳腺癌细胞系（MCF-10A和MCF-12A）的GA。相反，从人类乳腺癌细胞系（MCF-7，SK-BR-3，T-47D和MDA-MB-231）撤出血清和生长因子长达48小时，导致pSTAT3水平相对适度增加，并且C / EBPdelta基因表达并导致不同水平的GA。在大多数乳腺癌细胞系中，IL-6家族细胞因子治疗可增加pSTAT3水平和C / EBPdelta基因表达，但是，生长抑制是细胞系依赖性的。除了生长抑制途径中的“功能丧失”改变外，乳腺癌细胞系还在生长信号途径中表现出“功能获得”改变。 Akt生长/生存途径在T-47D和MCF-7乳腺癌细胞中被组成性激活。 Akt抑制剂LY 294,002通过血清和生长因子戒断或IL-6家族细胞因子治疗显着增强T-47D的生长抑制作用。最后，我们显示pSTAT3 / C / EBPdelta生长控制途径的激活与雌激素受体状态无关。这些结果表明，pSTAT3 / C / EBPdelta生长抑制信号转导途径中的“功能丧失”改变在人乳腺癌细胞系中相对普遍。 pSTAT3 / C / EBPdelta生长抑制信号转导途径的缺陷激活，与Akt生长刺激途径的组成性激活结合，可能在乳腺癌的病因或进展中起协同作用。

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